Maugeri, Caterina; (2002) Synthesis of new adjuvants and carriers for foot and mouth disease virus (fmdv). Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Foot and mouth disease virus (FMDV) is the etiological agent of an important disease in livestock. Despite the considerable amount of information accumulated in recent years, FMD still affects extensive areas of the world and is the most transmissible viral disease in animals: FMDV has been diagnosed in 34 countries during the past 18 months and 1,000 cases in the recent outbreak are accounted for in Great Britain alone. One of the difficulties in controlling FMDV is its occurrence in seven distinct serotypes and immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Vaccination is the first treatment against FMDV. The current vaccines consist of virus inactivated with imines and formulated with A1(OH)3/saponin (for ruminants) or incomplete oil-based formulations (for pigs and cattle). Based on previous results, a synthetic vaccine against FMDV was developed following the concept of adjuvant-carrier-epitope. Here we describe the synthesis and the development of novel synthetic adjuvants and carriers and their use in synthetic vaccines against foot and mouth disease virus. Different sets of lipophilic compounds were prepared in order to act as build-in adjuvants/carriers. They include cyclic and linear polyalcohols containing different numbers of alkylic chains. In-solution synthetic chemistry was used and separation and characterization of closely related lipid products, although successful, proved difficult. A synthetic dendrimeric polylysine carrier was also prepared but, following promising results of compounds lacking the MAP carrier, it was not linked to the constructs. The lipophilic constructs were then coupled to different copies of synthetic peptides corresponding to the VP1 (140-160) FMDV serotype C. Different kinds of synthetic liganding approaches were used for the conjugation, following the attachment of a residue of cysteine to the carboxy terminus of the peptides. The different approaches led to investigations of the role and the importance of different spacers between the adjuvant/carrier and the epitope.

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